AMP Parkinson's Disease and Related Disorders

Overview

In 2019, the National Institutes of Health (NIH) launched a collaboration with the Foundation for NIH (FNIH), the Food and Drug Administration (FDA), pharmaceutical and biotechnology companies, and non-profit organizations to facilitate therapeutic target validation from human samples and the discovery of new biomarkers for Parkinson’s disease (PD). In July 2024, this effort moved into its second phase with the launch of the Accelerating Medicines Partnership(R) in Parkinson’s Disease and Related Disorders (AMP(R) PDRD). This partnership builds on the foundation of AMP PD to find ways to better differentiate PD from related neurodegenerative disorders such as multiple system atrophy, Lewy body dementia, and progressive supranuclear palsy. The goal of this program is to enable earlier diagnoses, more timely interventions, and better outcomes for people living with these disorders.

About Parkinson’s Disease and Related Disorders

Parkinson’s disease is a chronic, progressive neurological disorder characterized by resting tremor, muscle rigidity, slowness of movement, impaired balance, and a shuffling gait. More recently, non-motor symptoms such as behavioral changes and cognitive impairment have also been associated with PD. Between 500,000 and 1 million Americans live with PD in the United States.

Individuals can develop a set of symptoms, including sleep disorders, constipation, and a decreased sense of smell, years or decades before motor symptoms appear. The root causes of PD remain unknown, but risk factors include age, genetics, and exposure to environmental hazards.

In addition to PD, several other disorders share similar pathologies to PD, which have been collectively referred to as “Parkinsonisms,” including 

• multiple system atrophy, which affects both the brain and spinal cord and is characterized by symptoms affecting both the central nervous system (e.g., movement) and the autonomic nervous system, which controls functions like blood pressure and digestion;
• Lewy body dementia, which is characterized by the presence of Lewy bodies, which contain alpha-synuclein, a protein also linked to PD, in the brain and results in cognitive decline that worsens over time; and 
• progressive supranuclear palsy, which is a rare disorder that affects body movements, walking and balance, and eye movements. The disorder can also affect mood, behavior, and thinking.

Need for New Biomarkers

Because PD results from the degeneration of nerves within the brain, early diagnosis is crucial for initiating treatments that can have the greatest impact. This diagnosis typically relies on the person’s medical history, imaging tests, and neurological exams that can help distinguish between PD and other conditions with similar symptoms..  A diagnostic test on cerebrospinal fluid, the alpha-synuclein seeding assay, has shown high accuracy in identifying persons with PD and even those with premonitory symptoms like REM sleep disorder.  Efforts to extend the accuracy of this test to more accessible samples like saliva, skin or blood are currently underway. 

A major focus of AMP PDRD is the identification of new biomarkers that can aid in the testing of new therapies in early phase clinical studies. These would include assays that differentiate among the different forms of Parkinsonism, that reflect ongoing pathologic changes in the nervous system, or that change in response to a targeted therapy. Measurements made from persons affected by Parkinsons whether from blood, brain, skin or other tissues are also valuable in confirming the validity of proposed new therapies, i.e., target discovery. 

The AMP PDRD Approach

As mentioned, AMP PDRD builds upon an earlier partnership, AMP PD, that consolidated data across multiple studies and made available a number of biosamples for research projects aimed at discovering and developing treatments for PD. This was made possible in large part due to the AMP PD Knowledge Platform, an online repository for data samples and analyses made available to the biomedical research community. This resource enables the broad sharing of validated and standardized data sets between research groups. 

AMP PDRD will expand these collections to include data from a wider range of people living with both PD and related disorders. This will aid in the identification of new biomarkers and targets for drug development and improve our ability to classify more precisely various disease stages and subtypes.

Goals

The goals of AMP PDRD are as follows:

1. The discovery and validation of PD and related synucleinopathy biomarkers
2. The integration of existing and new multi-omics data to identify molecular signatures within brain tissue and patient biosamples.
3. The establishment of a multi-scale analysis framework that leverages bioinformatics to create predictive modeling and analytical tools to identify and validate disorder subtypes.

PWLE Involvement and PD Advocacy Community

The AMP® PDRD project will 

1. Work closely with non-profit organizations like the Michael J. Fox Foundation (MJFF), Aligning Science Across Parkinson’s (ASAP), Parkinson’s Foundation, and others to gather insights from the Patient Advocacy groups for relevant and meaningful communication needs and opportunities to engage individuals with lived experience and caregivers as possible. 
2. Raise awareness among key audiences; highlight the launch and accomplishments of AMP® PDRD project among the research and Parkinson’s Disease advocacy and lived experience communities. 
3. Provide messaging tools to partners by developing easily tailored, customizable materials for the dissemination of key messages of AMP® PDRD project that they could use for their own purposes and channels, in their own words and with their own branding to help amplify outreach. 

Governance

AMP is a public-private partnership managed by the FNIH. NIH and industry partners share expertise and resources in an integrated governance structure that enables the best-informed contributions to science from all participants.

The AMP PDRD Steering Committee convenes monthly to discuss project plans and review ongoing progress and milestones. NINDS program staff members provide scientific and administrative direction and oversee the cooperative grants derived from the consortia. The steering committee also includes people with lived experience (PWLE) with Parkinson’s, and their direct input is included in all decisions made.

The AMP PDRD program has several working groups that bring together subject matter experts from academia and industry. Face-to-face meetings organized by FNIH provide an additional venue for communication and coordination.

Partners and Collaborators

NINDS Program Contacts for AMP® PDRD